DNA-Based Hybrid Catalysis

In Nature, DNA serves primarily as a storage medium for genetic information. Composed of four major monomers, it predominantly occurs in the form of a 

In addition to the major double-helical form, DNA also exists as triplexes and quadruplexes and forms complex three-way or four-way junctions. Single-stranded DNA has been shown in vitro to fold into complex, stable three-dimensional folds and to bind to smah molecules (such DNA molecules are named aptamers) or to catalyze reactions in a way similar to proteins (so-caUed deoxyribozymes or DNAzymes) [4]. This increased structural diversity makes it a more attractive host molecule for hybrid catalysis [5]. Furthermore, directed evolution approaches are easier to conduct with nucleic acids than with proteins, as nucleic acids can be directly rephcated and amphfied. 

The concept was soon expanded to other reactions, keeping salmon sperm DNA, Cu, and intercalating ligands (mostly dmbipy). Using these systems, asymmetric fluorinations, Michael and oxa-Michael additions, Friedel—Crafts reactions were reported, as well as a syn-hydration (in water), and an intramolecular cyclopropanation [6c, 8]. 

A detailed understanding of structure-function relations could not, however, be established so far in DNA-based hybrid catalysis. Likewise, applications in 

In contrast to the work described above, which involved mainly Lewis-acid catalysis, our laboratory had focused primarily on organometallic reactions in which the (transient) formation of a carbon-metal bond is instrumental to the process. Furthermore, we decided not to investigate intercalation-based systems, as they do not allow positional control of the DNA-metal interaction, thereby precluding 

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The first published reports on DNA-based hybrid catalysis are from Roelfes, Feringa, and coworkers [6]. They could demonstrate that DNA isolated from salmon sperm (an inexpensive commodity chemical) could dramaticahy influence the stereochemistry of the Cu -catalyzed DAR in water between an aza-chalcone and cyclopentadiene when used in combination with different aminoacridine-aminomethylpyridine conjugates (Figure 18.2). In these experiments, Cu ions act as Lewis acids and the aminomethylpyridine is a bidentate Cu chelator, while the acridine moiety intercalates into DNA and thereby brings the copper catalyst into the chiral environment. In their first report, the authors could achieve moderate enantioselectivities (up to 49% ee for the endo... 

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